Melatonin modulates glucocorticoid receptor mediated inhibition of antioxidant response and apoptosis in peripheral blood mononuclear cells

Autor: Amaresh Kumar Singh, Chandana Haldar
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
NF-E2-Related Factor 2
Blotting
Western
Apoptosis
Enzyme-Linked Immunosorbent Assay
Biochemistry
Peripheral blood mononuclear cell
Antioxidants
Dexamethasone
Melatonin
03 medical and health sciences
Receptors
Glucocorticoid
0302 clinical medicine
Endocrinology
Glucocorticoid receptor
Bcl-2-associated X protein
Immune system
Internal medicine
medicine
Animals
Immunoprecipitation
HSP90 Heat-Shock Proteins
Cell Shape
Molecular Biology
Cell Proliferation
bcl-2-Associated X Protein
Cell Nucleus
biology
Caspase 3
Goats
Hsp90
Germ Cells
030104 developmental biology
Leukocytes
Mononuclear
biology.protein
Interleukin-2
Biomarkers
Heme Oxygenase-1
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Glucocorticoid
medicine.drug
Zdroj: Molecular and Cellular Endocrinology. 436:59-67
ISSN: 0303-7207
DOI: 10.1016/j.mce.2016.07.024
Popis: Pineal melatonin is known for its immunomodulatory and anti-stress properties. It modulates stress condition by regulating antioxidant responses and apoptosis in the immune cells. Stress causes increased glucocorticoid level that acts through glucocorticoid receptor (GR) and is translocated into nucleus under regulation of HSP90 based chaperone machinery. Melatonin influences glucocorticoid and GR mediated stress condition in rodents, but till date there are no reports which could suggest the effect of melatonin treatment on GR mediated apoptosis and inhibition of Nrf-2/hemeoxygenase-1 (HO-1) induced antioxidant status in immunocompetent cells (peripheral blood mononuclear cells; PBMCs). Therefore, in the present study, we considered GR mediated inhibition of Nrf2 and HO-1 along with anti-apoptotic Bcl-2 expression in PBMCs. The PBMCs were treated with synthetic glucocorticoid; dexamethasone (Dex) and melatonin (Mel), to explore the effect of melatonin treatment in regulation of GR mediated apoptosis and inhibition of antioxidant status in immune cells. It was noted that melatonin treatment retained GR into cytoplasm by inhibiting the dissociation of HSP90 from GR-HSP90 complex and enhanced expression of Nrf2/HO-1 and Bcl-2 expression. This led to increased HO-1 expression and elevated Bcl-2 led to increased Bcl-2/Bax ratio that might ultimately enhanced the cellular antioxidant response and survival under glucocorticoid mediated stress condition. Our observations suggest that the declined GR nuclear translocation upon melatonin treatment might be responsible for the up-regulation of Nrf2 mediated HO-1 activity and increased Bcl-2/Bax ratio in PBMCs to maintain the immune homeostasis under stress condition.
Databáze: OpenAIRE
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